Hindawi Publishing Corporation Case Reports in Volume 2013, Article ID 931523, 6 pages http://dx.doi.org/10.1155/2013/931523

Case Report Diabetic Muscle : A Rare Cause of Acute Limb Pain in Dialysis Patients

G. De Vlieger,1 B. Bammens,1,2 F. Claus,3 R. Vos,4 and K. Claes1,2

1 Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium 2 Laboratory of Nephrology, Department of Microbiology and Imunology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium 3 Department of , University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium 4 Respiratory Division, University of Leuven and Department of Clinical Respiratory , Catholic University of Leuven, Herestraat 49, 3000 Leuven, Belgium

Correspondence should be addressed to G. De Vlieger; [email protected]

Received 18 March 2013; Accepted 7 April 2013

Academic Editors: J. Almirall, P. S. Passadakis, and H. Schiffl

Copyright © 2013 G. De Vlieger et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Diabetic muscle infarction is a rare microangiopathic complication occurring in patients with advanced mellitus. Diabetic patients with chronic kidney disease stage Vd are prone to develop this complication. The presenting symptom is a localized painful swelling of the affected limb. Symptoms usually resolve spontaneously during the following weeks, but frequent relapse can occur and in some cases swelling may lead to compartment syndrome. Biochemical blood analyses show an elevated C-reactive protein, but creatine kinase is often normal. Diagnosis can be made on clinical presentation and imaging, with magnetic resonance imaging as the gold standard. Histology is often not contributive. Treatment consists of rest, analgesics, rigorous glycemic control and low- dose . Severe cases of compartment syndrome require fasciotomy. In the current paper, we present two diabetic patients with cystic fibrosis, who are treated with automated peritoneal dialysis and suffered from episodic lower limb infarction. Wesubsequently review 48 episodes of diabetic muscle infarction previously reported in the literature in patients with end-stage renal disease.

1. Introduction (PD) was started. Two years later, she presented with acute pain in the right calf. Biochemical evaluation showed an Diabetic muscle infarction (DMInf) is a rare microangio- elevated creatine kinase (CK 218 U/L) and C-reactive protein pathic complication in patients with advanced diabetes melli- (CRP 97 mg/L). HbA1c was 5.8%. Ultrasound and computed tus (DM). Patients having terminal diabetic nephropathy are tomography (CT) showed diffuse muscular and subcuta- prone to develop DMInf and nearly one-fourth of DMInf, neous edema of the affected calf. Muscular biopsy demon- patients receive renal replacement treatment [1]. Conse- strated muscular atrophy, macrophages, and myophagia. The quently, nephrologists are likely to be increasingly confronted symptoms resolved within four weeks. There was a new onset with this disease entity. of pain in the left calf 18 months later. CK was normal, but CRP levels were elevated (215 mg/L). HbA1c was 7.2%. The 2. Case Reports clinical and biochemic characteristics are shown in Table 1. Magnetic resonance imaging (MRI) showed an infarction Case 1. A 27-year-old woman with cystic fibrosis started in the soleus muscle (Figures 1(a) and 1(b)). During the insulin treatment at the age of 11. When she was 16 years following days, pain increased and a compartment syndrome old, she received bilateral lung transplantation (SSLTx). Her was diagnosed by pressure measurement. A fasciotomy was immune-suppressive consisted of tacrolimus and performed, and low-dose aspirin was started with subse- steroids. At the age of 24, she developed chronic kidney quent resolution of the complaints in the following two disease stage V (CKD-Vd) for which peritoneal dialysis months. 2 Case Reports in Nephrology

(c)

(a)

(b) (d)

Figure 1: T2 weighted images with coronal (a, c) and axial (b, d) views for the 2 patients. The level of the axial views are indicated onthe coronal images by the dashed lines. Images (a) and (b) show diffuse edema in the calf muscles of the left lower limb of the first patient, as illustrated by the hyperintense signal of the muscular tissue (note the normal low signal intensity of the muscles in the right leg). Images (c) and (d) show similar changes in the adductor muscles of the left upper leg of the second patient.

Case 2. A 35-years-old woman with cystic fibrosis received 3. Discussion SSLTx at the age of 21. Redo SSLTx because of chronic lung allograftrejectionwasperformedsixyearslater.Immuno- DMInf was first described in 1965 by Angervall and Stener suppressive treatment consisted of tacrolimus and steroids. [2]. It is a rare microangiopathic complication in patients with DM was diagnosed at the age of 29, and subcutaneous advanced DM. The typical presentation is an acute onset of insulin treatment was initiated one year later. When she severe pain at rest, exacerbated by movement. Clinical exam- ination usually reveals a hard and warm palpable swelling of was 34 years old, PD was started. Six months later, she was the affected limb, and ultrasound is negative for DVT. admitted because of pain in the left thigh. The pain was In a review of 166 episodes in 115 diabetic patients by present during rest and increased during exercise. Clinical Trujillo-Santos, the mean age at presentation of DMInf was examination revealed a swollen and painful left upper leg with 42.6 years, and the mean duration of DM was 14.3 years absence of deep venous (DVT) on ultrasound. with 59% of the patients suffering from DM type17 1[ ]. MRIshowedmuscleinfarctionwithcentralnecrosisin A female predominance (61,5%) was observed, and associ- theadductors,medialvastusmuscle,andsartoriusmuscle ated microangiopathic complications included nephropathy, (Figures 1(c) and 1(d)). CRP was elevated (94 mg/L), but retinopathy, and neuropathy in 71.1, 56.6, and 54.5%, respec- CK’s were repeatedly normal. The DM was poorly controlled tively [17]. We described two patients with cystic fibrosis with an HbA1c of 8.7%. Low-dose aspirin was started, and who evolved to CKD-V after SSLTx. Both patients were thesymptomsresolvedaftersixweeks.Sixmonthslater, treated with PD and were at high risk for the development shewasreadmittedbecauseofseverepainintheright of DMInf due to multiple risk factors: DM type 1, admin- thigh. Biochemical examination showed an increased CRP of istration of calcineurin inhibitors and prothrombotic status 104 mg/L, the CK was within the normal range, and HbA1c due to uremia. Although there is no evidence of increased was 7,5%. MRI showed edema in the left pectineus muscle, thrombogenic risk in cystic fibrosis, lung transplantation external obturator, and adductor muscles. Analgesia was is clearly associated with a hypercoagulability [18]andan started with spontaneous resolution. increased risk for DVT and pulmonary embolism [19]. Case Reports in Nephrology 3 Right gastrocnemius Right gastrocnemius and soleus Right deltoid muscle Left biceps brachii Right thigh adductors (1) Left thigh (2) Right vastus medialis (3) Left thigh (4) Right calf Left rectus femoris Left quadriceps Left vastus lateralis (1) Left buttock (2) Right semitendinosus Left gastrocnemius Right rectus femoris Anterior right thigh Left vastus lateralis Bilateral quadriceps (1) Left vastus lateralis (2) Left calf (1) Left vastus medialis and intermedius (2) Right adductors (1) Right vastus lateralis (2) Left thigh (3) Left calf Left vastus muscles Right vastus medialis (1) Right thigh (2) Left calf (1) Left calf (2) Left gluteal region (3) Right thigh Left thigh (1) Left thigh (2) Right thigh (3) Right thigh Affected muscles Laboratory HbA1c CRP (mg/dL) CK (U/L) SPKSPK 5 —SPK —SPK 5.0 160 5.6 17 — — 21 Normal RRT IHD — — — IHDIHD — — 216 —IHD 381 IHD Elevated IHD — — — 35 300IHD — 289 — 692 463 70 Normal IHDIHD 12.4 — — — 649 350 IHD —IHD — — — — Normal APD 5.8 97 218 CAPD — — Elevated CAPD — — 556 CAPD — 105 Normal SPK, IHD 5.3 — 83 CAPD, IDH 7.9 214 — CAPD, IHD — — — CAPD, IHD — — Normal Table 1: Overview of reviewed cases in the literature. Neuropathy Retinopathy, neuropathy Retinopathy, coronaropathy Retinopathy, neuropathy, and ischemic cardiac disease Retinopathy, neuropathy Retinopathy, neuropathy Retinopathy, neuropathy — Retinopathy, neuropathy Retinopathy, neuropathy, and peripheral vascular disease Neuropathy — Retinopathy, neuropathy Retinopathy, neuropathy, and peripheral vascular disease Heart failure Retinopathy Retinopathy, peripheral vascular disease DM complications other than CKD Retinopathy, neuropathy, and peripheral vascular disease Retinopathy, coronary disease Retinopathy, neuropathy Retinopathy, neuropathy — Retinopathy, neuropathy 35 Female DM I 30 APD 8.7 94.2 97 24 Female DM I 11 4MlDI — ]49MaleDMII 5MlDI 35 ]55MaleDMII 5MlDI 31 ]55MaleDMII 5MlDI — ]51MaleDMII 2FmlDI8 9 7 ]29FemaleDMI 9 ]39FemaleDMI ]33FemaleDMI ]39FemaleDMI 3FmlDI16 ]31FemaleDMI 3MlDI 27 34 ]35MaleDMII ]49FemaleDMII 4MlDI— 41 25 ]49MaleDMI ]51MaleDMI — ]40MaleDMII ]49FemaleDMII ] 32 Male DM I 41 20 ]44FemaleDMII 3MlDI— ]31MaleDMI 39 ]39MaleDMII — — ]56FemaleDMII ]58MaleDMII 2FmlDI9 ]29FemaleDMI 3 4 5 6 7 4 4 4 8 8 9 5 8 7 9 10 8 11 12 13 5 5 Ref Age Gender[ Type DM[ Age at[ onset [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ 4 Case Reports in Nephrology Affected muscles Right gastrocnemius and soleus Right gastrocnemius and soleus (1) Left vastus medialis (2) Right thigh (3) Right calf Left triceps and forearm Right brachioradialis (1)Rightvastusmedialisandlateralis (2) Left thigh (3) Lefthamstrings (4) Lefthamstrings as kidney transplantation, IHD: intermittent hemodialysis, Laboratory HbA1c CRP (mg/dL) CK (U/L) KTx — — — RRT IHDIHD 8IHD 6.7IHD 6.2 136 9.5IHD — — — 23 — 1066 361 69 483 409 Table 1: Continued. — DM complications other than CKD Neuropathy, and ischemic heart disease Retinopathy, neuropathy Retinopathy Retinopathy, neuropathy Retinopathy, neuropathy, ischemic heart disease, and stroke 6MlDI — ]67MaleDMII 6FmlDI 45 ]61FemaleDMII 6MlDI 52 38 ]62MaleDMII ]63MaleDMII 6MlDI 43 ]61MaleDMII49 ]63MaleDMII 8 14 15 15 8 16 Ref Age[ Gender[ Type DM Age[ at onset [ [ [ DM: diabetes mellitus, CKD: chronic kidney disease, RRT: renal replacement therapy, APD: automated peritoneal dialysis, SPK: simultaneous pancre CAPD: continuous ambulatory peritoneal dialysis, KTx: kidney transplantation, CRP: C-reactive protein, and CK: creatine kinase. Case Reports in Nephrology 5

The two presented cases were treated with PD, but it is not with rest and analgesia alone. Surgical resection of the clear whether PD is associated with a higher risk to develop infarcted muscles increases the recovery period to 13 weeks DMInf compared to hemodialysis. Previous studies report [26] and is not a first-choice option. may a higher concentration of advanced glycation end products be beneficial, but it has also been reported that it causes (AGEs) that play an important role in the pathogenesis of worsening or relapse [27]. The short-term prognosis of the vasculopathy [20]. Moreover, conventional PD fluids contain muscle infarction is good since it is often a self-limiting glucose degradation products (GDP) that cause an increased disease. If a compartment syndrome is suspected, pressure production of AGEs [20]. In both of our patients, conven- measurement should immediately be performed with subse- tionalsolutionswereusedfromthestartofPDtreatment,and quently fasciotomy if the diagnosis is confirmed. Recurrence they were switched to a low GDP solution after a few months in the same or contralateral limb has been reported in 50 to because of infusion pain. It is tempting to speculate whether 62% of patients [6]. However, the overall survival of these theuseoflowGDPsolutionfromthestartcouldhaveavoided patients seems to be comparable with the prognosis after the DMInf. with a 55% 1-year survival rate in We reviewed the literature and discussed 48 episodes one report [28]. Due to the increase overall cardiovascular ofDMInfin30patientswithCKD-Vd[3–16]. Mean and mortality in CKD-V patients, the prognosis is probably worse median age at time of diagnosis of DM was 28.1 and 30.5 in our studied population. Consequently, treatment with years respectively, and DMInf occurred at a mean and median low-dose aspirin, rigorous glycemic control, and control ageof46.0and49.0years.Inourreview,therewasa of the serum phosphorus concentration is of paramount slight predominance for males (56.8%). Recurrent muscle importance. were reported in one third of the patients. Data In summary, we discussed the clinical presentation of comparing the different dialysis modalities were not available. two diabetic patients with recurrent episodes of DMInf after The most affected muscle groups were located in the upper leg initiation of peritoneal dialysis. Clinical and sonographic (68.8%) and lower leg (22.9%) only few (8.3%) were located in examination might suggest the diagnosis and is useful to the upper limb. Other diabetic complications were retinopa- rule out the presence of DVT. Contrast-enhanced MRI is thy (80.8%), neuropathy (69.2%), and macrovasculopathy the imaging modality of choice to confirm the diagnosis of (34.6%). muscle infarction and to screen for patients at risk to develop Symptoms of DMInf generally resolve spontaneously compartment syndrome. after an average of six weeks [21]. However, evolution to compartment syndrome might occur, warranting meticulous Conflict of Interests followup and prompt fasciotomy in severe cases. Biochemical evaluation shows increased CRP, and CK’s may be elevated The authors declare that they have no conflict of interests. during the early presentation. Later in the disease course, CK’s appear to be normal in most cases [22]. Consequently, References laboratory tests are not accurate in diagnosing DMInf. Sonographic examination typically demonstrates focal or [1] N. Melikian, J. Bingham, and D. J. A. Goldsmith, “Diabetic diffuse muscle edema of the affected limb and is in particular muscle infarction: an unusual cause of acute limb swelling in useful to exclude deep venous thrombosis [23]. CT can patients on hemodialysis,” American Journal of Kidney Diseases, detect muscular swelling and vascular calcifications, but is vol. 41, no. 6, pp. 1322–1326, 2003. not sensitive to detect early muscle (10). MRI has [2] L. Angervall and B. Stener, “Tumoriform focal muscular degen- a high tissue contrast resolution and is the ideal imaging eration in two diabetic patients,” Diabetologia,vol.1,no.1,pp. modality to depict muscular edema and pathological changes 39–42, 1965. in the fatty intramuscular septa, subfascial tissue, and the sub- [3]E.Theodoropoulou,E.Chelioti,K.Revenas,N.Katsilambros, cutis. The radiologic differential diagnosis of diabetic muscle A. Kostakis, and J. N. Boletis, “Diabetic muscle infarction after infarction includes an intramuscular abscess, myositis, and kidney and pancreas transplanation: case report and literature necrotizing fasciitis, and muscle biopsy might be necessary to review,” Transplantation Proceedings,vol.38,no.9,pp.3147– 3150, 2006. obtain a final diagnosis [24]. However, excisional biopsy and surgical debridement in these patients can be complicated [4] S.Delis,G.Ciancio,J.Casillasetal.,“Diabeticmuscleinfarction after simultaneous pancreas-kidney transplant,” Clinical Trans- by delayed wound healing, hematoma, infection, nerve palsy, plantation,vol.16,no.4,pp.295–300,2002. heterotopic calcification, and need for blood transfusion21 [ ]. [5] K. L. Lentine and S. S. Guest, “Diabetic muscle infarction in Inthemajorityofpatients,thediagnosisisbasedonthe end-stage renal disease,” Nephrology Dialysis Transplantation, clinical presentation and MRI findings, hence reducing the vol. 19, no. 3, pp. 664–669, 2004. need for biopsy and its associated complications. Evolution to [6]G.E.Umpierrez,R.G.Stiles,J.Kleinbart,D.A.Krendel,and a compartment syndrome has been described in a few cases. N. B. Watts, “Diabetic muscle infarction,” American Journal of Patients suffering from infarction of the thigh muscles are less Medicine,vol.101,no.3,pp.245–250,1996. prone to develop a compartment syndrome due to the larger [7] K. K. Madhan, P.Symmans, L. Te Strake, and W.van der Merwe, osteofascial envelope [25]. “Diabetic muscle infarction in patients on dialysis,” American Overall, treatment consists of rest, analgesia, and rigorous Journal of Kidney Diseases,vol.35,no.6,pp.1212–1216,2000. glycemic control. Low-dose aspirin shortens the recovery [8] C. Bingham, D. A. Hilton, and A. J. Nicholls, “Diabetic muscle time to 5.5 weeks as compared to 8.1 weeks in those treated infarction: an unusual cause of leg swelling in a diabetic on 6 Case Reports in Nephrology

continuous ambulatory peritoneal dialysis,” Nephrology Dialysis [27] C. S. Chester and B. Q. Banker, “Focal infarction of muscle in Transplantation,vol.13,no.9,pp.2377–2379,1998. diabetics,” Diabetes Care, vol. 9, no. 6, pp. 623–630, 1986. [9]K.M.Chow,C.C.Szeto,J.F.Griffith,T.Y.H.Wong,andP.K. [28]K.M.Chow,C.C.Szeto,T.Y.Wong,F.K.Leung,A.Cheuk, T. Li, “Unusual muscle pain in two patients with diabetic renal and P. K. Li, “Diabetic muscle infarction: myocardial infarct failure,” Hong Kong Medical Journal,vol.8,no.5,pp.368–371, equivalent,” Diabetes Care,vol.25,no.10,p.1895,2002. 2002. [10] S. R. Glauser, J. Glauser, and S. F. Hatem, “Diabetic muscle infarction: a rare complication of advanced diabetes mellitus,” Emergency Radiology,vol.15,no.1,pp.61–65,2008. [11] J. L. MacGregor, P. Chan, P. I. Schneiderman, and M. E. Gross- man, “Diabetic muscle infarction,” Archives of ,vol. 143, no. 11, pp. 1456–1457, 2007. [12]A.Pedicelli,P.Belli,M.Fratino,A.Cina,F.DiGregorio,and M. Rollo, “Diabetic muscle infarction,” American Journal of Medicine, vol. 111, no. 8, pp. 671–672, 2001. [13] L. Silberstein, K. E. Britton, F. P. Marsh, M. J. Raftery, and D. D’Cruz, “An unexpected cause of muscle pain in diabetes,” Annals of the Rheumatic Diseases,vol.60,no.4,pp.310–312, 2001. [14] S. Kapur, J. A. Brunet, and R. J. McKendry, “Diabetic muscle infarction: case report and review,” Journal of , vol.31,no.1,pp.190–194,2004. [15] R. Joshi, B. Reen, and H. Sheehan, “Upper extremity diabetic muscle infarction in three patients with end-stage renal disease: acaseseriesandreview,”Journal of Clinical Rheumatology,vol. 15,no.2,pp.81–84,2009. [16] R. Joshi and R. Vargas, “Diabetic muscle infarction in renal transplantation,” Transplantation,vol.77,no.2,p.321,2004. [17] A. J. Trujillo-Santos, “Diabetic muscle infarction: an underdiag- nosed complication of long-standing diabetes,” Diabetes Care, vol. 26, no. 1, pp. 211–215, 2003. [18] G. Izbichi, O. Bairey, D. Shitrit, J. Lahav, and M. R. Kramer, “Increased thrombpembolic events after lung transplantation,” Chest,vol.129,no.2,pp.412–416,2006. [19] H. A. Yegen, D. J. Lederer, R. G. Barr et al., “Risk factors for venous thromboembolism after lung transplantation,” Chest, vol. 132, no. 2, pp. 547–553, 2007. [20] N. J. McIntyre, L. J. Chesterton, S. G. John et al., “Tissue- advanced glycation end product concentration in dialysis patients,” Clinical Journal of the American Society of Nephrology, vol.5,no.1,pp.51–55,2010. [21] J. A. Morcuende, M. B. Dobbs, H. Crawford, and J. A. Buckwal- ter, “Diabetic muscle infarction,” The Iowa Orthopaedic Journal, vol. 20, pp. 65–74, 2000. [22] T. M. Kattapuram, R. Suri, M. S. Rosol, A. E. Rosenberg, and S. V. Kattapuram, “Idiopathic and diabetic necrosis: evaluation by magnetic resonance imaging,” Skeletal Radiology, vol. 34, no. 4, pp. 203–209, 2005. [23] L. O. Delaney-Sathy, D. P. Fessell, J. A. Jacobson, and C. W. Hayes, “Sonography of diabetic muscle infarction with MR imaging, CT, and pathologic correlation,” American Journal of Roentgenology,vol.174,no.1,pp.165–169,2000. [24] J. S. Jelinek, M. D. Murphey, A. J. Aboulafia, R. G. Dussault, P.A. Kaplan, and W. N. Snearly, “Muscle infarction in patients with diabetes mellitus: MR imaging findings,” Radiology,vol.211,no. 1, pp. 241–247, 1999. [25] A. L. Smith and P. W. Laing, “Spontaneous tibial compartment syndrome in Type 1 diabetes mellitus,” Diabetic Medicine,vol. 16,no.2,pp.168–169,1999. [26] S. Kapur and R. J. McKendry, “Treatment and outcomes of diabetic muscle infarction,” Journal of Clinical Rheumatology, vol.11,no.1,pp.8–12,2005. Copyright of Case Reports in Nephrology is the property of Hindawi Publishing Corporation and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.